Author, as appears in the article.: López-Cano C, Gutiérrez-Carrasquilla L, Barbé F, Sánchez E, Hernández M, Martí R, Ceperuelo-Mallafre V, Dalmases M, Fernández-Veledo S, Vendrell J, Hernández C, Simó R, Lecube A

Department: Medicina i Cirurgia Ciències Mèdiques Bàsiques

URV's Author/s: Ceperuelo Mallafré, Maria Victoria / Fernandez Veledo, Sonia / Vendrell Ortega, Juan José

Keywords: Type 2 diabetes Sleep Rhythms Night Metabolic control Hypoxia Endocrine Clock genes Circadian clock Chronodisruption Cellular adaptation Apnea

Abstract: Limited reports exist on the relationships between regulation of oxygen homeostasis and circadian clock genes in type 2 diabetes. We examined whether the expression of Hypoxia-Inducible Factor-1 alpha (HIF-1 alpha) and HIF-2 alpha relates to changes in the expression of clock genes (Period homolog proteins (PER)1, PER2, PER3, Retinoid-related orphan receptor alpha (RORA), Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL), Circadian locomotor output cycles kaput (CLOCK), and Cryptochrome proteins (CRY) 1 and CRY2) in patients with type 2 diabetes. A total of 129 subjects were evaluated in this cross-sectional study (48% with diabetes). The gene expression was measured by polymerase chain reaction. The lactate and pyruvate levels were used as surrogate of the hypoxia induced anaerobic glycolysis activity. Patients with diabetes showed an increased plasma concentration of both lactate (2102.1 +/- 688.2 vs. 1730.4 +/- 694.4 uM/L,p= 0.013) and pyruvate (61.9 +/- 25.6 vs. 50.3 +/- 23.1 uM/L,p= 0.026) in comparison to controls. However, this finding was accompanied by a blunted HIF-1 alpha expression (1.1 (0.2 to 5.0) vs. 1.7 (0.4 to 9.2) arbitrary units (AU),p <= 0.001). Patients with diabetes also showed a significant reduction of all assessed clock genes' expression. Univariate analysis showed that HIF-1 alpha and almost all clock genes were significantly and negatively correlated with HbA1c concentration. In addition, positive correlations between HIF-1 alpha and the clock genes were observed. The stepwise multivariate regression analysis showed that HbA1c and clock genes independently predicted the expression of HIF-1 alpha. Type 2 diabetes modifies the expression of HIF-1 alpha and clock genes, which correlates with the degree of metabolic control.

Thematic Areas: Medicine, general & internal Medicine (miscellaneous) Medicine (all)

licence for use: https://creativecommons.org/licenses/by/3.0/es/

Author's mail: sonia.fernandez@urv.cat victoria.ceperuelo@urv.cat juanjose.vendrell@urv.cat

Author identifier: 0000-0003-2906-3788 0000-0002-4460-9761 0000-0002-6994-6115

Record's date: 2023-10-07

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://www.mdpi.com/2077-0383/9/8/2632

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Journal Of Clinical Medicine. 9 (8): 1-10

APA: López-Cano C, Gutiérrez-Carrasquilla L, Barbé F, Sánchez E, Hernández M, Martí R, Ceperuelo-Mallafre V, Dalmases M, Fernández-Veledo S, Vendrell J, He (2020). Effect of Type 2 Diabetes Mellitus on the Hypoxia-Inducible Factor 1-Alpha Expression. Is There a Relationship with the Clock Genes?. Journal Of Clinical Medicine, 9(8), 1-10. DOI: 10.3390/jcm9082632

Article's DOI: 10.3390/jcm9082632

Entity: Universitat Rovira i Virgili

Journal publication year: 2020

Publication Type: Journal Publications